Quest for space: Tenacity of DNA, Protein, and Lipid macromolecules in intracellular crowded environment

The biochemical processes in the cellular milieu involving biomacromolecular interaction usually occur in crowded and heterogeneous environments, impacting their structure, stability, and reactivity. The crowded environment in vivo is typically ignored for experimental investigations since the studies get complex due to intracellular biophysical interactions between nucleic acids, proteins, cellular membranes, and various cations/anions present in the cell. Thus, being a ubiquitous property of all cells, studying those biophysical aspects affecting biochemical processes under realistically crowded conditions is of prime importance. Crowders or crowding agents are usually exploited to mimic the in vivo conditions on interacting with such genomic species, revealing structural and functional changes resulting from excluded volume and soft interactions. In the last few years, studies including crowders of varied sizes have gained attention concerning the consequences of crowding agents on biomolecular structural transitions and stability. This review comprehensively summarizes macromolecular crowding, emphasizing the biophysical effects and contribution of soft interactions in the heterogeneous cellular environment.